Fourth Quarter 2025 Financial Results & Business Update February 12, 2026 On Today's Call • Welcome Brendan Strong, SVP, Investor Relations • Overview Richard Paulson, President and Chief Executive Officer • Pipeline Update Dr. Reshma Rangwala, Chief Medical Officer and Head of Research • Commercial Highlights and Myelofibrosis Commercial Opportunity Sohanya Cheng, Chief Commercial Officer and Head of Business Development • Financial Results and Guidance Lori Macomber, Chief Financial Officer and Treasurer ...

Core Viewpoint - Karyopharm Therapeutics Inc. will report its fourth quarter and full year 2025 financial results on February 12, 2026, and will host a conference call to discuss these results and other updates [1]. Company Overview - Karyopharm Therapeutics Inc. is a commercial-stage pharmaceutical company focused on pioneering novel cancer therapies, particularly through oral compounds that address nuclear export dysregulation, a key mechanism in oncogenesis [3]. - The company's lead compound, XPOVIO (selinexor), is a first-in-class oral exportin 1 (XPO1) inhibitor approved in the U.S. for three oncology indications and has received regulatory approvals in over 50 territories, including the EU, UK (as NEXPOVIO), and China [3]. - Karyopharm has a focused pipeline targeting high unmet need cancers, including multiple myeloma, endometrial cancer, myelofibrosis, and diffuse large B-cell lymphoma (DLBCL) [3].

Core Insights - Karyopharm Therapeutics anticipates a transformative year in 2026, with significant data readouts from two Phase 3 trials expected, which could redefine treatment standards in myelofibrosis and endometrial cancer [2][10] Financial Performance - Preliminary unaudited total revenue for 2025 is estimated at approximately $145 million, with U.S. XPOVIO net product revenue expected to be around $115 million [1][14] - The company completed strategic financing transactions that extended its cash runway beyond the expected top-line readout of the Phase 3 SENTRY trial [14] Clinical Trials and Developments - The Phase 3 SENTRY trial for myelofibrosis has completed enrollment with 353 patients, evaluating selinexor in combination with ruxolitinib [6][17] - Top-line data from the SENTRY trial is expected in March 2026, which could significantly impact patient outcomes [2][10] - The Phase 3 XPORT-EC-042 trial for endometrial cancer is on track to report top-line data in mid-2026, focusing on a biomarker-driven patient population [2][20] Market Position and Strategy - Demand for XPOVIO remained consistent in 2025 compared to 2024, with approximately 60% of overall net product revenue driven by the community setting [6] - Global patient access for selinexor expanded in 2025, with favorable reimbursement decisions in Spain and China, and approvals in over 50 countries [6][24] Product Information - XPOVIO (selinexor) is a first-in-class oral exportin 1 inhibitor approved for multiple oncology indications, including multiple myeloma and diffuse large B-cell lymphoma [24][29] - The company is actively preparing for regulatory filings and commercialization efforts related to its ongoing clinical trials [2][10]

Clinical Trial Updates - Phase 3 SENTRY试验的顶线数据预计在2026年3月公布[8, 25] - Phase 3 XPORT-EC-042子宫内膜癌试验的顶线数据预计在2026年中期公布[8, 67] - 评估SPd治疗复发性多发性骨髓瘤患者的3期全球研究(XPORT-MM-031/EMN29)的顶线数据预计在2026年上半年公布[70, 73] - SENTRY (XPORT-MF-034) 是一项针对JAKi初治骨髓纤维化患者，Selinexor联合Ruxolitinib的3期试验，已于2025年9月完成患者招募，共353名患者[23, 24] Commercial Performance - 2025年第三季度，美国XPOVIO净产品收入为3200万美元，比2024年第三季度的2950万美元增长8.5%[37] - 公司重申2025年全年净产品收入指导范围为1.1亿美元至1.2亿美元[37, 54] - 社区环境持续驱动约60%的美国整体净产品收入[37] Financial Highlights - 2025年第三季度总收入为4400万美元，高于2024年第三季度的3880万美元[51] - 预计现有流动资金，在计入2025年10月8日宣布的融资交易的影响后，足以支持公司计划运营至2026年第二季度[53] - 研发和SG&A费用预计为2.35亿美元至2.45亿美元[54] Myelofibrosis Market Opportunity - Selinexor联合Ruxolitinib疗法在美国市场可能达到每年约10亿美元的净销售额峰值[41, 43] - 约75%的患者有意愿接受联合治疗[42]

Core Insights - Karyopharm Therapeutics reported a total revenue of $44.0 million for Q3 2025, an increase from $38.8 million in Q3 2024, with U.S. net product revenue from XPOVIO (selinexor) at $32.0 million, reflecting an 8.5% increase year-over-year [1][11][19] - The company reaffirmed its full-year 2025 total revenue guidance of $140 million to $155 million and U.S. XPOVIO net product revenue guidance of $110 million to $120 million [1][14] - The Phase 3 SENTRY trial for myelofibrosis has completed enrollment, with top-line data expected in March 2026 [2][8] Financial Performance - Total revenue for Q3 2025 was $44.0 million, compared to $38.8 million in Q3 2024 [11] - U.S. net product revenue was $32.0 million, up from $29.5 million in Q3 2024, driven by gross-to-net favorability [6][11] - License and other revenue increased to $12.0 million in Q3 2025 from $9.3 million in Q3 2024, primarily due to milestone-related revenue from Menarini [12] - R&D expenses decreased to $30.5 million in Q3 2025 from $36.1 million in Q3 2024, attributed to lower clinical trial costs [13] - SG&A expenses were $26.6 million in Q3 2025, down from $27.6 million in Q3 2024, reflecting cost reduction initiatives [16] Clinical Development - The Phase 3 SENTRY trial for myelofibrosis enrolled 353 patients and is evaluating selinexor in combination with ruxolitinib [6][22] - The company continues to enroll patients in the Phase 3 XPORT-EC-042 trial for endometrial cancer, with top-line data expected in mid-2026 [10][26] - Enrollment in the Phase 3 XPORT-MM-031 trial for multiple myeloma was completed in Q4 2024, with data expected in the first half of 2026 [7][13] Cash Position and Outlook - As of September 30, 2025, the company had cash, cash equivalents, and investments totaling $46.2 million, down from $109.1 million at the end of 2024 [20][43] - The company expects its existing liquidity will be sufficient to fund operations into Q2 2026 [14]

Core Insights - Karyopharm Therapeutics has secured $100 million in financing to enhance financial flexibility and extend its cash runway into Q2 2026, supporting ongoing clinical trials and operations [1][5][10] - Preliminary total revenue for Q3 2025 is expected to be between $42 million and $44 million, with U.S. XPOVIO net product revenue projected at approximately $32 million [6][7] - The company is on track to report top-line data from the Phase 3 SENTRY trial in myelofibrosis by March 2026 [1][9] Financing Transactions - The financing includes a private placement of 1,487,917 shares of common stock and warrants to purchase 1,317,771 shares at an exercise price of $6.64, expected to generate approximately $8.75 million in gross proceeds [2][3] - The company will issue a total of 7,223,982 new shares and various warrants, with a reduction in the exercise price of existing warrants from $16.50 to $6.64 [3][5] - The financing aims to comply with Nasdaq rules and is structured to strengthen the balance sheet and equitize near-term debt maturities [1][3] Clinical Trials and Programs - The Phase 3 SENTRY trial is evaluating selinexor in combination with ruxolitinib for myelofibrosis, with co-primary endpoints focused on spleen volume reduction and symptom score improvement [13] - Enrollment is ongoing in the Phase 3 XPORT-EC-042 trial for endometrial cancer, with top-line data expected in mid-2026 [9][17] - Karyopharm's lead compound, selinexor, is positioned as a potential first combination therapy for myelofibrosis, aiming to redefine treatment standards [1][15] Financial Position - Prior to the financing, Karyopharm reported approximately $46 million in cash and equivalents as of September 30, 2025 [7][8] - The financing transactions are expected to provide significant financial flexibility, including $67.5 million in new capital and deferrals of interest and royalty payments [5][10]

Core Insights - Karyopharm Therapeutics has completed enrollment in the Phase 3 SENTRY trial, which is evaluating the combination of selinexor and ruxolitinib in patients with myelofibrosis [1][2] - The trial aims to provide top-line data in March 2026, with the potential for selinexor plus ruxolitinib to become the first approved combination therapy for myelofibrosis [2] - Myelofibrosis is a rare blood cancer affecting approximately 20,000 patients in the U.S. and 17,000 in the EU, with current treatment options limited to JAK inhibitors [3] Company Overview - Karyopharm Therapeutics is a commercial-stage pharmaceutical company focused on developing novel cancer therapies, particularly through its lead compound, XPOVIO (selinexor), which is an oral exportin 1 (XPO1) inhibitor [5][12] - XPOVIO is approved in the U.S. for multiple oncology indications and has received regulatory approvals in various countries, including the EU and China [6][12] - The company is advancing its pipeline to address high unmet needs in cancers such as multiple myeloma, endometrial cancer, and diffuse large B-cell lymphoma [12] Clinical Trial Details - The SENTRY trial enrolled 353 patients and evaluates a once-weekly dose of 60 mg of selinexor in combination with ruxolitinib compared to placebo plus ruxolitinib [2] - Co-primary endpoints include spleen volume response rate of 35% at week 24 and average change in absolute total symptom score over 24 weeks [2] - The trial targets JAKi-naïve myelofibrosis patients with platelet counts greater than 100 x 10/L, with a randomization ratio of 2-to-1 favoring the selinexor arm [2] Industry Context - Myelofibrosis is characterized by bone marrow fibrosis, leading to anemia and other debilitating symptoms, with current treatments often resulting in transfusion dependence [3] - The myelofibrosis community is in need of new therapies, as existing JAK inhibitors have limitations, including a high discontinuation rate due to anemia [3] - The development of new combination therapies like selinexor plus ruxolitinib could significantly impact treatment paradigms for myelofibrosis patients [2][3]

Financial Performance & Guidance - Karyopharm's Q2 2025 U S net product revenue was $29 7 million, a 6% increase from $28 0 million in Q2 2024[69] - The company anticipates full year 2025 U S XPOVIO net product revenue to be between $110 million and $120 million[69] - Karyopharm projects total revenue between $140 million and $155 million for 2025, with R&D and SG&A expenses ranging from $240 million to $250 million[88] Myelofibrosis (MF) Program - Selinexor has a peak U S revenue opportunity of up to ~$1 billion in myelofibrosis, pending positive data and regulatory approval[9, 19, 70] - In a Phase 1 trial, 79% of patients achieved SVR35 (spleen volume reduction of 35% or more) at week 24 with selinexor plus ruxolitinib[28] - Preliminary extrapolated data from the Phase 3 SENTRY trial suggests a potentially more favorable safety profile for selinexor plus ruxolitinib compared to ruxolitinib alone, with Grade 3+ anemia rates potentially lower at ~26% compared to 37%[35, 37] - Top-line data from the Phase 3 SENTRY trial of selinexor in myelofibrosis is expected in March 2026[9, 33] Endometrial Cancer (EC) Program - The company is focusing the Phase 3 XPORT-EC-042 trial on patients with TP53wt EC who are pMMR or dMMR and medically ineligible for checkpoint inhibitors[46] - Top-line data from the Phase 3 XPORT-EC-042 trial in endometrial cancer is anticipated in mid-2026[91] Multiple Myeloma (MM) Program - Enrollment is complete in the Phase 3 XPORT-MM-031 trial evaluating SPd in patients with previously treated multiple myeloma (n~120)[60] - Top-line data from the Phase 3 XPORT-MM-031 trial in multiple myeloma is expected in the first half of 2026[93]

Myelofibrosis Opportunity - Karyopharm is focused on the transformative myelofibrosis opportunity in 2025, building on its foundation in multiple myeloma[4,10] - The peak annual revenue opportunity for selinexor in myelofibrosis is estimated to be up to approximately $1 billion[4,12] - In a Phase 1 trial, 78.6% of intent-to-treat patients achieved SVR35 (spleen volume reduction of 35% or more) at week 24 with selinexor 60 mg + ruxolitinib[24] - In the Phase 1 trial, the average improvement in Absolute TSS (Total Symptom Score) was 18.5, suggesting a positive outcome for the SENTRY Phase 3 trial[31,32] - Selinexor meaningfully decreased transfusion burden by approximately 50% compared to physician's choice in the XPORT-MF-035 trial[58] Endometrial Cancer Opportunity - Karyopharm is focusing the Phase 3 XPORT-EC-042 trial on patients with TP53wt EC (endometrial cancer) that are pMMR or dMMR and medically ineligible to receive a checkpoint inhibitor[74] - Data from the SIENDO trial showed an encouraging signal of long-term median PFS (progression-free survival) benefit of 28.4 months in the TP53 wild-type subgroup[78] - In the SIENDO Trial, the median PFS benefit was 39.5 months in the TP53 Wild-Type/pMMR Subgroup[81] Commercial and Pipeline Strategy - XPOVIO net product revenue in 2024 was approximately $113 million[11] - The company aims to maintain its profitable commercial foundation in the competitive multiple myeloma marketplace and drive increased XPOVIO revenue in 2025[91] - The company is actively enrolling patients in the Phase 3 SENTRY trial in myelofibrosis, with top-line data expected in late 2025/early 2026[4,39,40] - The company is actively enrolling patients in the Phase 3 XPORT-EC-042 trial in endometrial cancer, with top-line data anticipated in mid-2026[85,88]

Myelofibrosis Opportunity - Karyopharm is focused on the transformative myelofibrosis opportunity in 2025, with a peak annual revenue opportunity of up to approximately $1 billion[4, 12] - The company expects top-line data from the Phase 3 SENTRY trial of selinexor in myelofibrosis in late 2025/early 2026[4] - Data from a Phase 1 trial showed that 78.6% of intent-to-treat patients achieved SVR35 at week 24 with selinexor 60 mg + ruxolitinib[24] - In the Phase 1 trial, the average improvement in Absolute TSS (Abs-TSS) was 18.5, suggesting a positive outcome with Abs-TSS can be achieved in the SENTRY Phase 3 trial[33] Clinical Trial Data and Development - The Phase 2 XPORT-MF-035 trial showed that spleen volume reduction rates more than doubled with selinexor compared to physician's choice, with 33% achieving SVR35 compared to 13%[48, 49] - In the XPORT-MF-035 trial, patients who progressed on physician's choice (Rux) and received selinexor showed a meaningful spleen volume reduction[51] - Selinexor meaningfully decreased transfusion burden by approximately 50% in the XPORT-MF-035 trial[59] - The SENTRY (XPORT-MF-034) Phase 3 trial of selinexor in combination with ruxolitinib in JAKi naïve myelofibrosis has passed futility analysis and continues as planned, with top-line data expected in late 2025/early 2026[39, 41] Endometrial Cancer - Karyopharm is focusing the Phase 3 XPORT-EC-042 trial on patients with TP53wt EC that are pMMR or dMMR and medically ineligible to receive a checkpoint inhibitor[75] - Data from the SIENDO trial (ASCO 2024) showed an encouraging signal of long-term median PFS benefit of 39.5 months in the TP53 Wild-Type/pMMR subgroup[82]